Genetic Study Maps 88,127 Metabolic Links in 619,372 People, Challenging BCAA Diabetes Theory
Updated
Updated · Nature.com · May 20
Genetic Study Maps 88,127 Metabolic Links in 619,372 People, Challenging BCAA Diabetes Theory
2 articles · Updated · Nature.com · May 20
A meta-analysis of 249 circulating metabolic traits in up to 619,372 people found 88,127 locus-trait associations across 8,398 loci, greatly expanding the genetic map of human metabolism.
The scale let researchers fine-map 3,000 putative causal variants and show that 19.4% of confidently fine-mapped signals were low-frequency variants, which were about twice as likely as common variants to alter coding or splicing.
Using colocalization and cis-Mendelian randomization, the study linked plasma lactate signals at GP6, GRK5 and ZFPM2 to pulmonary embolism risk through platelet activation, suggesting lactate is a biomarker rather than a direct cause.
The same analyses found that lowering branched-chain amino acids through the BCAA catabolism pathway is unlikely to materially reduce type 2 diabetes risk, despite earlier observational and genome-wide associations.
Researchers released the summary statistics and browsing tools publicly, while noting 97% of samples were of mainly European ancestry, limiting discovery in underrepresented groups.
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